Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human interleukin-3 (IL-3) receptor is constitutively expressed on certain hematopoietic cells where it mediates proliferation and differentiation, or functional activation. We have recently found that human umbilical vein endothelial cells (HUVECs) also express IL-3 receptors and that the expression is enhanced by stimulation with the monokine tumor necrosis factor alpha. In this report we show that the lymphokine interferon gamma (IFN gamma) is a powerful stimulator of the IL-3 receptor of HUVECs and that the combination of IL-3 and IFN gamma has a synergistic effect on major histocompatibility complex (MHC) class II expression and on the production of the early-acting hematopoietic cytokines IL-6 and granulocyte colony-stimulating factor (G-CSF). IFN gamma caused a time- and dose-dependent up-regulation of mRNA for both the alpha and beta chains of the IL-3 receptor, with maximal effects occurring 12 to 24 hours after stimulation with IFN gamma at 100 U/mL. Induction of mRNA correlated with protein expression on the cell surface, as judged by monoclonal antibody staining of both receptor chains and by the ability of HUVEC to specifically bind 125I-labeled IL-3 (125I-IL-3). Scatchard analysis of HUVECs stimulated with IFN gamma at 100 U/mL for 24 hours showed approximately 6,300 IL-3 receptors per cell that were of a high affinity class (dissociation constant [kd] = 500 pmol/L) only. The addition of IL-3 to IFN gamma-treated HUVECs strongly enhanced the expression of MHC class II antigen. Importantly, IFN gamma and IL-3 also exhibited a synergistic effect in the induction of the mRNA for G-CSF and IL-6. This was reflected in increased amounts of G-CSF and IL-6 protein in HUVEC supernatants. In contrast, IFN gamma and IL-3 did not stimulate granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-8 production in HUVECs. These results show that IFN gamma is a strong stimulator of IL-3 receptor expression in HUVECs and suggest that in vivo T-cell activation, causing the concomitant production of IFN gamma and IL-3, may lead to enhanced endothelial MHC class II expression and to the selective production of early-acting hematopoietic cytokines. Thus, IL-3 could influence immunity and hematopoiesis by acting not only on hematopoietic cells, but also on vascular endothelium.
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PMID:Interferon-gamma upregulates interleukin-3 (IL-3) receptor expression in human endothelial cells and synergizes with IL-3 in stimulating major histocompatibility complex class II expression and cytokine production. 754 Aug 83

The effects of various cytokines on MHC class II antigen expression were examined in murine microglia. Interleukin-3 (IL-3), as well as interferon-gamma (IFN-gamma), induced MHC class II antigen expression on these cells. IL-3 additionally enhanced MHC class II antigen expression induced by IFN-gamma. The induction of MHC class II antigen expression by IL-3 was not mediated via IFN-gamma production, because the effect was not blocked by antibodies to IFN-gamma. In contrast, granulocyte-macrophage colony-stimulating factor (GM-CSF) did not affect the expression of MHC class II antigen on naive cells and down-regulated IFN-gamma-mediated induction of MHC class II antigen expression on microglia. Because IL-3 and GM-CSF are apparently produced in the central nervous system, MHC class II antigen expression on microglia may be regulated by these cytokines synthesized in the central nervous system.
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PMID:Induction of MHC class II antigen expression on murine microglia by interleukin-3. 782 62

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) are weak inducers of major histocompatibility complex (MHC) class II expression on purified human blood monocytes. The glucocorticoid dexamethasone synergizes with GM-CSF or IL-3 for the upregulation of HLA-DR, -DP and -DQ antigen mRNA and cell-surface expression by these cells. The purpose of the present study was to address the mechanism of dexamethasone action. We demonstrate that the capacity of dexamethasone to up-regulate GM-CSF-induced MHC class II expression correlates with the capacity to up-regulate GM-CSF receptor, but not the interferon-gamma (IFN-gamma) receptor, in a highly dose-dependent manner on monocytes. Although dexamethasone induces GM-CSF receptor expression, it does not confer responsiveness to IL-5, a cytokine that shares a common chain of its heterodimeric cytokine receptor signalling molecule with IL-3 and GM-CSF. Three other steroid hormones, beta-oestradiol, vitamin D3 and dehydroepiandosterone (DHEA), were also tested for their capacity to up-regulate MHC class II expression. All three mediators failed to enhance MHC class II expression or GM-CSF receptor expression on the surface of human monocytes. These experiments suggest that dexamethasone may act to up-regulate GM-CSF-induced MHC class II antigen expression on monocytes by up-regulating cytokine receptor expression.
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PMID:Dexamethasone up-regulates granulocyte-macrophage colony-stimulating factor receptor expression on human monocytes. 783 47

In all tissues that have been studied to date, dendritic leucocytes constitute only a small proportion of total cells and are difficult both to isolate and purify. This study reports on a method for the propagation of large numbers of dendritic cells (DC) from mouse spleen using granulocyte-macrophage colony-stimulating factor (GM-CSF) and their characteristics. Within a few days of liquid culture in GM-CSF, B10 BR (H-2k, I-E+) mouse splenocytes formed loosely adherent myeloid cell clusters. Mononuclear progeny released from these clusters at and beyond 4 days exhibited distinct dendritic morphology and strongly expressed leucocyte common antigen (CD45), CD11b, heat-stable antigen, Pgp-1 (CD44) and intercellular adhesion molecule-1 (ICAM-1; CD54). The intensity of expression of the DC-restricted markers NLDC 145 and 33D1, the macrophage marker F4/80, and Fc gamma RII (CDw32) was low to moderate, whereas the cells were negative for CD3, CD45RA and NK1.1. High and moderate levels, respectively, of cell surface staining for major histocompatibility complex (MHC) class II (I-Ek) and the B7 antigens (counter-receptors of CTLA4, a structural homologue of CD28) were associated with potent stimulation of unprimed, allogeneic T cells (B10; H-2b, I-E-). DC propagated in a similar fashion from DBA/2 mouse spleen proved to be strong antigen-presenting cells (APC) for MHC-restricted, syngeneic T-helper type 2 (Th2) cell clones specifically responsive to sperm whale myoglobin. Footpad or intravenous injection of GM-CSF-stimulated B10.BR spleen-derived DC into B10 (H-2b, I-E-) recipients resulted in homing of the allogeneic cells to T-cell-dependent areas of lymph nodes and spleen, where they strongly expressed donor MHC class II antigen 1-2 days later. These findings indicate that cells can be propagated from fresh splenocyte suspensions that exhibit distinctive features of DC, namely morphology, motility, cell-surface phenotype, potent allogeneic and syngeneic APC function and in vivo homing ability. Propagation of DC in this manner from progenitors present in lymphoid tissue provides an alternative and relatively convenient source of high numbers of these otherwise difficult to isolate but functionally important APC.
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PMID:Generation of DC from mouse spleen cell cultures in response to GM-CSF: immunophenotypic and functional analyses. 789 Feb 96

Cytotoxicity is an important function of the immune system that results in destruction of cellular targets by humoral and cellular mechanisms. The functional capacity of granulocytes, lymphocytes and macrophages are of significance for cancer patients because of the ability of these cells to exhibit anti-tumor activity. The hallmark of immune cytotoxicity is the recognition and destruction of selected targets by humoral and cellular effects that distinguish between targets and normal cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine with potential to be an anti-neoplastic cytokine. GM-CSF induces: (1) differentiation of monocytes to large macrophage like cells; (2) augmentation of MHC class II antigen expression on monocytes; (3) enhancement in vitro of macrophage and granulocyte natural cytotoxicity and ADCC; and (4) increased expression of adhesion molecules and granulocytes and monocytes. GM-CSF also cooperates with other cytokines in the expansion of specific T cells. Several experimental and clinical studies have demonstrated the anti-neoplastic effects of GM-CSF alone or in combination with cytokines or/and monoclonal antibody. Interestingly, the future might see the combination of GM-CSF and mouse monoclonal antibody MAb17-1A in the adjuvant setting in colon- and/or rectal carcinoma patients.
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PMID:Anti-tumoral effect of GM-CSF with or without cytokines and monoclonal antibodies in solid tumors. 910 76